Resistance to IL-10 inhibition of interferon gamma production and expression of suppressor of cytokine signaling 1 in CD4+ T cells from patients with rheumatoid arthritis.

Jiro Yamana, Masahiro Yamamura, Akira Okamoto, Tetsushi Aita, Mitsuhiro Iwahashi, Katsue Sunahori, Hirofumi Makino

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction.

Original languageEnglish
Pages (from-to)R567-577
JournalArthritis research & therapy
Volume6
Issue number6
Publication statusPublished - 2004

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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